This research is based on the hypothesis that cell-surface molecules play critical roles in the development and regulation of differentiating systems such as spermatogenesis. To explore this hypothesis, cell surface differentiation antigens of spermatogenesis are being recognized and defined using monoclonal antibodies from hybrids derived by fusion of normally-immunized lymphocytes and a myeloma cell line. Two antigens have been defined and explored in detail. They are both testis specific, not on liver, kidney, brain, spleen or whole ovary. In addition, they are species specific to the mouse, but not strain specific, and are trypsin sensitive and collagenase insensitive. The two antigens appear to be expressed in different but overlapping time windows during spermatogenesis.